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    A combinatorial method to enable detailed investigation of protein-protein interactions

    Maclagan, K. and Tommasi, R. and Laurine, E. and Prodromou, C. and Driscoll, P.C. and Pearl, L.H. and Reich, S. and Savva, Renos (2011) A combinatorial method to enable detailed investigation of protein-protein interactions. Future Medicinal Chemistry 3 (3), pp. 271-282. ISSN 1756-8919.

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    Abstract

    Background: Successful structural investigations of protein-protein interactions can be facilitated by studying only the core interacting regions of the constituent proteins. However, attempting the discovery of stable core complexes using informed trial-and-error approaches can prove time and resource intensive. Methods: We describe a valuable extension of combinatorial domain hunting (CDH), a technology for the timely elucidation of soluble protein truncations. The new method, CDH2, enables empirical discovery of stable protein-protein core complexes. CDH2 is demonstrated ab initio using a previously well-characterized Hsp90/Cdc37 complex. Results: Without using a priori information, we demonstrate the isolation of stable protein-protein complexes, suitable for further analyses. Discussion: This resource-efficient process can provide protein complexes for screening of compounds designed to modulate protein-protein interactions, thus facilitating novel drug discovery.

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